The objective of t his program is to expand and strengthen the capabilities of Florida A&M University (FAMU) investigators in biomedical research, to provide undergraduate students with "hands-on" experience in the fundamentals of scientific research and to motivate them to pursue biomedical research careers, as well as to train graduate students in state of the art research in the biomedical sciences with concentration in pharmacology, medicinal chemistry, biochemistry, molecular biology, physiology and toxicology. The proposed research program will involve studies using laboratory animals. The subprojects have the following topics: (1) Metabolism based Rational Drug Design-Synthesis and Evaluation of Haloperidol Analogs (2) Loss of L-dopa Efficacy Related to Induction of Enzymes of Methylation (3) Skin Surface Temperature Gradients and Shivering in Coronary bypass Patients (4) Cellular and Biochemical Adaptations of Neuropeptide FF Associated with Opiate Tolerance (5) A Molecular Genetic Analysis of the Role of S-Adenosyl L-Methionine in Parkinson's Disease (6) The L-Arginine/Nitric Oxide Pathways of Mast Cells and Eosinophils (7) Development of Urinary Biomarkers of Cadmium Exposure and Intoxication (8) Diabetes Induced Alteration in Met-Encephalon Synthesis (9) Synthesis and Evaluation of Safer Anti-inflammatory Steroids (10) Intraperitoneal Estradiol Delivery Systems for Osteoporosis Therapy (11) Synthesis and Biological Activity Determinations of Some N- aminotetrahydropyridines (12) Biodegradable Nanocapsules for the Delivery of Monensin as a Potentiator of Immunotoxins (13) Developing an Animal model for Response to Pentobarbital (14) Neonatal Lead Exposure Effects on the Adrenal Cortex Function and (15) Neurochemical Basis of the Beneficial Effects of Chronobiotic Drugs.